Stress is a basic fact of life. In its broadest sense, it can be conceived of as any environmental event challenging homeostasis. Developing effective means for coping with stress, in many ways, differentiates successful from unsuccessful species. A dominant "stress response" in man is the activation of the hypothalamic-pituitary-adrenal axis. The humoral concomitants to this response are complex and not well characterized. Key elements include hypothalamic stimulatory secretogogues, CRH and anti-diuretic hormone, the hypothalamic inhibitory secretogogues, endogenous opiates, somatostatin, the natriuretic peptides, and oxytocin, POMC and its products, ACTH, MSH, and beta- endorphin; and the products of adrenal secretion, primarily cortisol in the human being. How these molecules orchestrate the HPA response to stress and the nature of the beneficial effects of this phenomenon are poorly understood. More clearly understood are the "stress-related disorders"' reproductive failure in adults and retarded growth in children. Since both of these abnormalities can be consequences of glucocorticoid excess, it is tempting to speculate that it is the cortisol component of the stress response that is responsible for these adverse effects. This proposal will use the cortisol production rate as a marker for stress and examine the hypothesis that chronic stress plays an important etiologic role in many cases of "idiopathic" infertility in adults and "idiopathic" growth retardation in children. The cortisol production rate will be measured with a new techniques using a deuterated cortisol infusion followed by the measurement of plasma cortisol "isotope enrichment" by LC-mass spectroscopy. The techniques is without radiation hazard and safe for women and children. Groups of patients bridging the spectrum from mild to severe stress will be studied in each category, as will their responses to therapeutic intervention. The results of this study should shed new light on the pathophysiology of "stress-related" disorders, and may indicate new avenues for diagnosis and treatment.